0 Survey of Human Genome shows proof of Evolution

Genome researchers at the University of Chicago have identified more than 700 regions in human DNA where apparently strong selection has occurred, driving the spread of genes linked to a broad range of characteristics.

"These are very recent events?within the past ten thousand years," said Jonathan Pritchard, a geneticist whose laboratory team conducted the study.

The results suggest that humans in different regions have continued to adapt in numerous ways to both environmental changes and cultural innovations.

Many of the genetic changes Pritchard's group detected came during or after the emergence of agriculture, beginning about 10,000 years ago, and long after the formation of modern human populations.

Some of the genes most strongly affected by selection were those associated with skin color, bone structure, and the metabolism of different foods.

Using newly available data, the scientists conducted a genome-wide scan for genetic variants showing evidence of recent selection in European, Asian, and African populations.

Most of the selected genes varied strongly among the three groups, suggesting that humans were adapting to pressures specific to different parts of the world.

The results are published in this month's issue of the journal PLoS Biology.

Changing World, Changing Genes

Positive selection occurs when a specific gene gives its carriers some advantage over others who lack the gene.

The methods used by Pritchard's group detected apparently beneficial genes that have spread through a large portion of the population but are not yet universal.

The findings, along with other recent studies, begin to provide a kind of genetic narrative of recent human evolution.

Joshua Akey, a genetics researcher at the University of Washington in Seattle, says selection-driven changes recorded in the genome provide tantalizing clues about past challenges faced by humans.

"Recent human history was a time of rapid change in population size, diet, pathogen exposure, and culture," Akey said.

"These are all potentially strong selective forces, which Dr. Pritchard and his colleagues appear to have captured in their analysis."

For example, major changes in diet occurred as nomadic hunter-gatherers slowly shifted to a settled agricultural existence.

Pritchard says this transition left a legacy of strong selection on genes associated with the processing of carbohydrates and fatty acids.

The clearest example?one previously known about by researchers?is the gene that allows for the digestion of milk into adulthood.

Among Europeans, whose ancestors relied on milk products as an important food source, this gene has become widespread. In most other human populations the gene is rare.

The study also provides new evidence that mutations to better digest different food products have spread in other groups.

Asian and African populations showed selection in genes affecting the metabolism of the plant sugars mannose and sucrose.

All three groups also showed selection for different genes involved in the uptake, storage, and energy conversion of dietary fats.

Another previously unreported example of natural selection involves the genes that people today rely on to process most pharmaceutical products.

Changes in these genes may be a legacy of human exposure to toxic plant compounds, either through a diet of wild foods or deliberate medicinal uses.

Physical Differences

Genes related to physical characteristics also showed strong evidence of selection, with interesting differences among the three populations.

"We found five different genes involved in skin pigmentation in the European population," Pritchard said.

He noted that, for humans living far from the equator, lighter skin is important for producing vitamin D, which is often formed in the body following exposure to the sun's ultraviolet rays.

Pritchard says evidence of recent pigmentation changes in Europeans may be the tail end of a much older process underway since modern humans first moved out of Africa or Asia to higher latitudes.

But the genetic changes could also be a reflection of more recent northward migrations following the last Ice Age, about 14,000 years ago, he says.

The survey also turned up evidence of selection in genes affecting skeletal development in Europeans and Asians and hair formation in Africans.

Pritchard says that while proteins involved in these processes were clearly targeted, it is still too early to say exactly why the changes occurred or what the evolutionary outcomes may have been.

Disease Selection

Evidence of different selective pressures operating on different populations may be medically important, says study lead author Benjamin Voight.

Discovering genes that contribute to common human diseases is always difficult, Voight said.

But "our hope is that the identification of selective targets using evolutionary theory might give other researchers a starting point."

Many disease-related genes should leave a strong signal of selection, because they influence individual survival.

By examining how selection has operated on different populations, researchers may be able to track down the genes underlying conditions such as diabetes, hypertension, and obesity, which vary in incidence and severity across ethnic groups.

"This research may provide the foundation for understanding how human evolutionary history has contributed to the susceptibility to complex diseases," the University of Washington's Akey said.

"Genome-wide scans for selection are not an end but rather an exciting beginning."